Biomedical Engineering Reference
In-Depth Information
those of dextran [96], and silan coatings are also resistant to enzymatic attacks in
lysosomes. In an
in vitro
study [98], Jordan and colleagues inoculated carcinomas
(colonic, adenocarcinoma and glioma) and normal human cell controls (fi broblasts
and neurons) with dextran- and aminosilan-coated magnetites. The results showed
a greater cell kill with aminosilan-coated magnetites with an alternating magnetic
fi eld compared to a water bath treatment
in vitro
. The same authors also used these
particles to create hyperthermia after directly injecting them into human prostate
cancer xenografts [99, 100] and brain tumor xenografts [101]
in vivo
. Both trials
involved direct injection inside the tumor mass of an orthotopic Dunning rat
model. Following particle administration, prostate cancer growth was signifi cantly
inhibited, with the prostate glands retaining 82.5% of the injected iron at 10 days
after intratumoral application, and enabling sequential thermal therapies to be
performed without the repeated injection of nanoparticles.
The fi ndings of Jordan and coworkers prompted a series of clinical studies with
aminosilan-coated particles, these being the fi rst reported clinical applications of
interstitial hyperthermia using magnetic nanoparticles in locally recurrent pros-
tate cancer. The study results showed that a single intratumoral application of
aminosilan-coated particles was retained in the prostate gland during the 6-week
treatment. A recent Phase I clinical trial showed that intracranial thermotherapy
using magnetic nanoparticles could be safely applied at therapeutic temperatures,
with local effi cacy and no adverse side effects [102]. Other clinical trials investigat-
ing the use of magnetic nanoparticles to deliver interstitial hyperthermia have
included a Phase I study with hepatocellular carcinoma (HCC), esophageal cancer,
and local residual tumors of different entities (cervical, uterine and ovarian carci-
nomas, as well as sarcomas), and also Phase II trials of prostate cancer and
glioblastoma.
7.4.1.3
Magnetic Cationic Liposomes
In 1999, Kobayashi and coworkers [103] developed magnetic cationic liposomes to
facilitate uptake by tumor tissue. These liposomes showed a 10-fold greater affi nity
towards glioma cells than did neutral, unsubstituted magnetite liposomes, due to
the positive charge of the magnetic cationic liposome interacting electrostatically
with the negatively charged glioma cells [104]. In an
in vitro
study of rat glioma
and agar phantoms subjected to a high-frequency magnetic fi eld (118 kHz), the
temperature rose to more than 43 °C, and all cells died after 40 min period of
irradiation due to the nanoparticles' hypothermic effect [104].
Other experiments have been conducted to investigate the effi cacy of magnetic
cationic liposome-mediated hyperthermia in animals with several types of tumor,
including B16 mouse melanoma [105] , T - 9 rat glioma [106] , osteosarcoma in
hamsters [107], MM46 mouse mammary carcinoma [108], PLS 10 rat prostate
cancer [109], and VX-7 squamous cell carcinoma in rabbit tongue [110]. Although
several
in vivo
studies have been conducted - including one in which frequent,
repeated hyperthermia caused a complete regression of mouse mammary carci-
noma which was initially
>
15 mm in size [110] - no clinical studies have yet been
conducted.
